The present invention relates generally to a method of manufacturing drug delivery and drug container devices, such as syringe components, and packaging the components in a clean, substantially particulate-free area. More particularly, the invention is directed to a method for manufacturing glass or plastic syringe barrels and assembling and packaging the syringe barrels in a clean room or locally controlled environment which is clean and substantially free of airborne particulates.
Drug delivery devices are generally prepared by molding or shaping the various components and then assembling the components. The assembling steps and other processing operations typically produce a device that subsequently must be cleaned to remove particulates adhering to the surfaces to satisfy cleanliness standards for drug delivery devices. After cleaning, the drug delivery devices are packaged and sterilized.
Syringes have been classified into several general types. The first type is assembled and placed in sterile packaging which can be shipped with a vial or ampoule of a drug or other injectable solution. The vial or ampoule is generally made of glass or other clear material that does not interfere with the stability of the drug during prolonged storage. The syringe is filled with the drug or other solution at the point of use and injected into the patient. Another type of syringe is packaged with a vial filled with a powdered or lyophilized drug which is dissolved in water or other suitable solvent prior to charging into the syringe.
These syringes have the disadvantage of increasing the time and difficulty of filling the syringe at the point of use with increased possibility of contamination of the syringe and/or drug solution. There is a further risk of glass particles from the ampoules contaminating the drug solution when the ampoules are opened.
Several of these disadvantages are overcome by providing prefilled syringes which can be filled with a suitable drug solution prior to use. Prefilled syringes, as the term is known in the art, are syringes that are filled by the drug manufacturer and shipped to the health care provider ready for use. Prefilled syringes have the advantage of convenience and ease of application with reduced risk of contamination of the drug solution. A difficulty in producing prefilled syringes, if they are made of plastic rather than glass, is selecting suitable materials that maintain their clarity for extended periods of time and do not contaminate or react with the drug solution.
Syringes and other drug delivery devices are generally assembled and packaged in clean rooms to maintain proper cleanliness levels. The clean rooms are equipped with extensive filter assemblies and air control systems to remove particulates and pyrogens from the air in the room and to prevent particulates and pyrogens from entering the room. The operators and other personnel in the clean room are required to wear appropriate protective garments to reduce contamination of the air and the drug delivery devices being manufactured or assembled. As people and equipment enter and leave the clean room, the risk of contamination and introduction of foreign particulates and pyrogens increases.
Various operations are able to form clean and sterile drug delivery devices. However, subsequent handling, filling and printing of the drug delivery device can contaminate the device. It is then necessary to clean and sterilize the drug delivery device before use.
Accordingly, there is a continuing need in the industry for an improved system for manufacturing and assembling clean and sterile medical devices and filling such devices.
The present invention is directed to a method and apparatus for maintaining a clean environment during the manufacture and assembly of medical devices such as drug delivery devices and medical container devices. More specifically, the invention is directed to the manufacture of various medical containers, drug delivery and drug container devices which are clean and have a low bio-burden or are sterile at the completion of the manufacturing step and immediately transferring the devices to a clean room or to a locally controlled environment to maintain cleanliness levels while assembling and packaging the devices. The medical devices can be filled with a suitable substance such as, saline solutions, flush solutions or contrast agents, pharmaceutical agents and vaccines, in either a dry or liquid state.
Accordingly, a primary object of the invention is to manufacture medical container devices immediately upstream of at least one housing assembly which defines a locally controlled environment. The medical containers are manufactured from glass or plastic under conditions which produce a substantially clean and sterile part. The housing assembly receives the medical containers directly from the manufacturing apparatus without a prior cleaning step so that the containers can be assembled within the housing assembly under controlled conditions to maintain predetermined cleanliness standards for medical containers and devices.
Another object of the invention is to provide a method for manufacturing a substantially clean and low bio-burden medical containers, such as a syringe barrel and assembling the syringe barrel with various components, such as a tip closure or Luer lock, in a locally controlled environment without the need for a water washing step.
A further object of the invention is to provide a method and apparatus for forming glass medical containers, such as drug delivery devices or components, annealing the glass medical containers, and then immediately capturing the annealed container in an environmentally controlled area to maintain a predetermined cleanliness and low bio-burden. The annealed glass medical containers are captured from the annealing oven in a manner to maintain the cleanliness and low bio-burden to avoid a mandatory cleaning step. The environmentally controlled area can be a clean room or a locally controlled environment.
Another object of the invention is to provide a method and apparatus for producing clean medical containers and delivering the devices to a housing assembly which defines a locally controlled environment, where the housing assembly includes a HEPA filter and a fan or blower to feed filtered air into the housing and maintain the housing assembly at predetermined cleanliness levels.
In embodiments of the invention, the medical containers are glass syringe barrels, and particularly prefillable glass syringe barrels, manufactured by processes which produce substantially clean and low bio-burden or sterile syringe barrels. The glass syringe barrels are made from cylindrical glass tubes that are cut to a desired length. The tubes are then fed to a forming machine which in one embodiment heats the ends of the tubes and forms a flange at one end and a tip at the opposite end. The glass syringe barrels are annealed by heating in a Lehr or annealing oven to at least about 560xc2x0 C. for an appropriate time to relieve stresses in the glass. The annealing produces a clean and low bio-burden syringe barrel which is then immediately transferred to an environmentally controlled area substantially without contamination.
A further object of the invention is to provide a housing assembly which maintains a locally controlled environment for assembling medical containers and packaging an array of medical containers in closed second containers. The medical containers can be sterilized in a subsequent step.
The housing assembly defining the locally controlled environment can be a portable unit having a work surface for performing the desired operations manually or automatically. The work surface is enclosed by side panels, at least some of which are preferably transparent to allow viewing and inspection by an operator located outside the housing. The assembly includes a top wall coupled to the side panels to define an enclosure. The assembly includes a fan or blower assembly and a filter assembly to direct filtered air into the housing and maintain a clean environment and can be operated to maintain a positive pressure in the housing assembly to prevent the infiltration of unfiltered air. An optional exhaust fan can also be provided to draw air downwardly through the housing assembly and exhaust the air without causing a negative pressure in the housing assembly.
In one embodiment of the invention, the medical containers exit the forming device and are immediately captured in an environmentally controlled area to maintain cleanliness. The medical devices, such as syringe barrels, in the housing assembly optionally can be cleaned by streams of clean filtered air or ionized air when necessary. The cleaning air removes substantially all particulates that may be adhered to the inner and outer surfaces of the barrel to attain the desired cleanliness level. A vacuum exhaust can be provided in the area of the barrel to carry the particulates away from the barrel and out of the housing assembly. Tip closures, Luer locks or syringe needles with their associated needle sheaths are also supplied to the housing assembly where they can be cleaned with filtered air or ionized air. The tip closures, Luer locks and needles are coupled to the syringe barrels. A lubricant is preferably applied to the inner surface of the syringe barrel, and the syringe barrels are placed in a grid or tray which is in turn placed in a container such as a tub. A plastic sheet is placed over the tray and the tub is closed with a sheet of flexible material which generally is heat-sealed to the tub. The tub is then enclosed in an outer wrap such as a plastic bag which is heat sealed. The tub, outer wrap and contents are sterilized by a sterilizing gas or radiation. Some or all of these operations can be conducted in a single housing assembly or in a plurality of housing assemblies coupled together.
A method of producing prefillable, glass syringe barrels in accordance with the present invention comprises the steps of supplying a glass tube to a forming device and forming a hollow syringe barrel having a flange at one end and a tip at the other end. The syringe barrels are annealed in a Lehr oven, cooled, and received in a first housing assembly having an air filtering device to maintain a predetermined cleanliness level therein, and a plurality of tip closures are supplied to the first housing assembly and are assembled with the syringe barrels. A stream of filtered air is directed to the syringe barrels and syringe components to remove particulates therefrom and clean the outer surfaces thereof. The assembled syringe barrels and syringe components are conveyed to a second housing assembly having a filtering device for maintaining a predetermined cleanliness level, and a lubricant is preferably applied to the inner surfaces of the syringe barrels. In a third housing assembly, the syringe barrels are formed into an array and placed into a container having a closed bottom, side walls and an open top. Thereafter, the container is conveyed to a fourth housing assembly having an air filtering device to maintain a predetermined cleanliness level, and a closure is applied to the container to seal the container.
The aspects of the invention are further attained by providing a method of producing a filled syringe comprising the steps of forming a plastic syringe barrel in an injection molding machine where the syringe barrel has a cylindrical side wall, an open proximal receiving end and a frustoconically shaped outlet nozzle at its distal end and transferring the syringe barrel, without any additional cleaning or sterilization, into an environmentally controlled area to maintain a predetermined cleanliness level. A stream of filtered air is directed toward the syringe barrel in the environmentally controlled area to remove particles from surfaces thereof to clean the syringe barrel. A tip cap is delivered to the environmentally controlled area and the tip cap is assembled onto the outlet nozzle of the syringe barrel to close the outlet nozzle and the syringe barrel is filled with a substance through its open proximal end. A stopper is delivered to the environmentally controlled area and is inserted into the open proximal end of the barrel to form a prefilled syringe. The prefilled syringe is then removed from the environmentally controlled area. In further embodiments, a stopper is applied to the syringe followed by filling the syringe through the tip or nozzle and then closing with a tip cap.
These and other aspects, advantages and salient features of the invention will become apparent to one skilled in the art from the annexed drawings and the following detailed description which discloses preferred embodiments of the invention.